Congenital hypopigmentary diseases (“albinism”) result from a defect in the synthesis or distribution of melanin pigment [1]. Melanin is responsible for skin, hair, and eye pigmentation. It is synthesized from the amino acid tyrosine in special organelles, the melanosomes. Different forms of albinism are due to mutations in genes involved in melanin production and accumulation [2]. Ocular albinism (OA) affects primarily the eye; oculocutaneous albinism (OCA) affects the skin and hair in addition [1].
Ocular Albinism Type I (OA1; MIM 300500) is the most common OA form [1]. OA1 is transmitted as an X-linked trait, with affected males showing the complete phenotype and heterozygous carrier females showing only minor signs of the disease. Visual abnormalities in OA1 are similar to those present in all forms of albinism [1, 3]. OA1 male patients have reduced visual acuity, which represents a major handicap, nystagmus, strabismus and marked photophobia [1]. This results from a developmental disorder of the retina characterized by foveal hypoplasia and misrouting of the optic fibers at the chiasm [3]. In addition, unlike other forms of albinism, the OA1 retinal pigment epithelium (RPE) and, to a lesser extent, the skin melanocytes present with characteristic large pigment granules, the macromelanosomes, suggesting that abnormal melanosomal biogenesis might occur in OA1 [4-6].
The gene responsible for OA1 (OA1) has been identified by positional cloning [7]. It encodes an orphan G-protein coupled receptor (OA1), which crosses the melanosomal membrane. Oa1 is expressed exclusively in RPE and skin melanocytes [8-12] and its transcript is detectable in murine embryonic RPE since early stages of development [10].
Gene transfer holds great promises for the treatment of inherited retinal diseases [16, 17]. Vectors based on adeno-associated viruses (AAV) are able to stably and efficiently transduce the retina of animal models of retinal diseases and their toxicity and efficacy will be soon evaluated in the human retina [18-20]. It has been shown that AAV vectors with an AAV1 capsid (AAV2/1) efficiently transduce the murine RPE [21-23], thus representing important tools for the treatment of animal models of RPE defects, such as Oa1−/− mouse.
Retinal electrophysiological function has been analyzed in albino (OCA) rodents and abnormalities in both light-evoked responses and ability to recover from photoreceptor desensitization following bright light exposure (dark adaptation) have been described [24-27].